tbuckley/cabot-search huggingface dataset:
Abstract 1469: 14-3-3 binding during G1 stabilizes and sequesters PTOV1 to the cytoplasm
Authors: Katie L. Pennington, Colten M. McEwan, James Woods, Colin M. Muir, A G Pramoda Sahankumari, Riley Eastmond, Eranga R. Balasooriya, Christina M. Egbert, Katherine K. McCormack, Joshua L. Andersen
Journal: Cancer Research (2022)

Abstract Cells must respond to changing environments by modulating signaling and gene expression patterns to maintain homeostasis, health, and viability. Inappropriate responses lead to disease processes, such as cancer. Despite improvements in targeted treatment options, cancer remains the second leading cause of death in the United States, illustrating the need to develop new highly effective targeted therapies. 14-3-3 interacts with a network of proteins to support signaling pathways promoting oncogenesis, metastasis, growth, cellular survival, and chemoresistance in a variety of cancers, including lung, prostate, and breast. We recently identified prostate tumor overexpressed 1 (PTOV1) as a novel 14-3-3 interacting protein promoting tumorigenic gene expression patterns. We showed that 14-3-3 binding sequesters PTOV1 in the cytoplasm and protects PTOV1 from proteasomal degradation. Using double thymidine block synchronization, we now demonstrate that both PTOV1 phosphorylation and total PTOV1 levels peak in G1, prior to PTOV1 translocating into the nucleus during S phase. These data support our model that 14-3-3-PTOV1 binding maintains PTOV1 in the cytoplasm during G1, where it is stabilized to carry out translational regulation. As the cell enters S phase, loss of phosphorylation and the accompanying loss of 14-3-3 binding allows PTOV1 to translocate into the nucleus, carry out relevant nuclear functions, and then be degraded via the proteasome. Citation Format: Katie L. Pennington, Colten M. McEwan, James Woods, Colin M. Muir, A G Pramoda Sahankumari, Riley Eastmond, Eranga R. Balasooriya, Christina M. Egbert, Katherine K. McCormack, Joshua L. Andersen. 14-3-3 binding during G1 stabilizes and sequesters PTOV1 to the cytoplasm [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1469.
Abstract 5193: Case report: Long-term response to Camrelizumab in a pretreated metastatic mixed testicular germ cell tumor patient
Authors: Hui Zhang, Da Jiang, Erhong Meng, Wenya Song, Xue Zhang
Journal: Cancer Research (2022)

Abstract Introduction: To date, very limited information is available about the efficacy of immune checkpoint inhibitor (ICI) therapy in mixed testicular germ cell tumor (TGCT) or variations of DNA damage repair (DDR) genes as predicators for it. Case presentation: We reported a 19-year-old male patient with pretreated metastatic mixed TGCT harboring 5 variations in the BRCA2, MSH6 and PMS2 genes detected using plasma-based circulating tumor DNA (ctDNA). He obtained a durable clinical benefit from single-agent Camrelizumab (a PD-1 inhibitor), with the progression-free survival (PFS) of over 19 months and overall survival (OS) of over 6 years. Conclusion: To the best of our knowledge, this case is the first study of long-term benefit from ICI in a pretreated mixed metastatic TGCT patient harboring 5 variations of DDR genes detected using ctDNA. Table 1. Genomic profile of the patient. Gene Transcript Exon Nucleotide change Alteration Mutant allele frequency/copy number (%) Sequencing depth (×) Medication guides CDH1 NM_004360 exon 15 c.2382delC p.V794fs 0.98 1018 Sensitive to bicalutamide FBXW7 NM_018315 exon 11 c.1761delG p.G587fs 1.88 1009 Sensitive to mTOR inhibitor BCR NM_004327 exon 19 c.3311C&amp;gt;G p.A1104G 1.92 1148 BCR NM_004327 exon 19 c.3316G&amp;gt;A p.D1106N 9.25 1124 BCR NM_004327 exon 22 c.3611C&amp;gt;G p.A1204G 2.29 918 BCR NM_004327 exon 22 c.3615G&amp;gt;A p.T1205T 2.05 926 BCR NM_004327 exon 22 c.3684T&amp;gt;C p.P1228P 2.3 1000 BRAF NM_004333 exon 1 c.64G&amp;gt;A p.D22N 54.15 301 BRCA2 NM_000059 exon 15 c.7522G&amp;gt;A p.G2508S 49.21 1138 CDH1 NM_004360 exon 2 c.144A&amp;gt;G p.R48R 0.7 1001 CYP2B6 NM_000767 exon 5 c.785A&amp;gt;G p.K262R 35.63 595 FCGR3A NM_000569 exon 4 c.634T&amp;gt;G p.F212V 99.75 810 FGFR1 NM_015850 exon 15 c.2017C&amp;gt;T p.R673W 0.84 958 FGFR1 NM_015850 exon 15 c.1991G&amp;gt;T p.W664L 0.25 815 LRIG3 NM_153377 exon 16 c.2589G&amp;gt;A p.T863T 48.91 1143 MSH6 NM_000179 exon 10 c.4006G&amp;gt;T p.V1336F 8.31 349 PMS2 NM_000535 exon 9 c.932A&amp;gt;G p.H311R 0.27 1109 PMS2 NM_000535 exon 9 c.934A&amp;gt;G p.M312V 0.44 1131 PMS2 NM_000535 exon 15 c.2570G&amp;gt;C p.G857A 69.81 573 ROS1 NM_002944 exon 29 c.4783T&amp;gt;C p.L1595L 50.62 1051 SMO NM_005631 exon 3 c.582A&amp;gt;G p.E194E 48.98 1223 TSC2 NM_000548 exon 41 c.5209C&amp;gt;A p.P1737T 1.04 866 Citation Format: Hui Zhang, Da Jiang, Erhong Meng, Wenya Song, Xue Zhang. Case report: Long-term response to Camrelizumab in a pretreated metastatic mixed testicular germ cell tumor patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5193.
Abstract 125: The role of oxidative stress on the polyaneuploid cancer cell state in metastatic cancer
Authors: Melvin Li, Sarah R. Amend, Kenneth J. Pienta
Journal: Cancer Research (2022)

Abstract Metastatic cancer is responsible for 90% of cancer deaths and is currently incurable due to resistance to all systemic anticancer therapies. Our lab hypothesizes that this resistance is driven by a subpopulation of cells in the tumor that enter the polyaneuploid cancer cell (PACC) state by undergoing a polyaneuploid transition (PAT). Cells in the PACC state are found in cell culture, xenograft, and genetically engineered mouse models, as well as in clinical samples. We have shown that cancer cells are induced to undergo a PAT upon exposure to external stress, such as chemotherapeutic treatments that include platinum-based therapy, etoposide, and taxane drugs. In addition, cells that enter the PACC state are resistant to that stress. One mechanism of therapy-induced cancer cell death is due to the resultant oxidative stress. We hypothesize that this oxidative stress drives a subset of cancer cells to undergo the PAT, thus enabling them to persist following treatment. To test the effects of oxidative stress on the PACC state, we treated cancer cells with cisplatin to induce the PAT and measured mitochondrial function and levels of reactive oxygen species (ROS). Using fluorescence microscopy with live-cell mitochondrial and ROS dyes, we showed that cells in the PACC state have higher mitochondrial mass, exhibit two to three times more mitochondrial activity per total mitochondria, and have over a five-fold increase in intracellular ROS levels per unit area when compared to typical cancer cell populations that they arise from. Moreover, PACCs exhibit a three-fold increase in their oxygen consumption rate and have higher expression of genes related to mitochondrial respiration and antioxidant pathways when compared to cells that did not undergo the PAT. Taken together, this suggests that cells in the PACC state may have a higher tolerance for stress since they can withstand higher amounts of ROS that result from both therapy and mitochondrial activity without exhibiting cell death. Our goal is to investigate how oxidative stress affects PACC formation and identify mechanisms of how PACCs manage stress to ultimately target these cells. If we can prevent PACC formation or find a method to eliminate cells in the PACC state, we can attack and resolve the issue of therapeutic resistance and incurability of metastatic cancer. Citation Format: Melvin Li, Sarah R. Amend, Kenneth J. Pienta. The role of oxidative stress on the polyaneuploid cancer cell state in metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 125.
Abstract 740: Obesity promotes liver pro-oxidative and DNA damage in mammary tumor of Zucker rats
Authors: Reza Hakkak, Stepan Melnyk, Soheila Korourian
Journal: Cancer Research (2022)

Abstract Obesity is a major health problem in the US and world. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, and certain types of cancers such as breast cancer. Our laboratory reported that obesity increased mammary tumor model using obese Zucker rat model. However, the effects of obesity in the liver in regard to oxidative stress and DNA reaction is less known. In present study, we used a DMBA induced-mammary tumor model to further investigate the effects of obesity on creation of pro-oxidative environment in liver and oxidative DNA reaction. Lean and obese female rats were at 50 days of age received 7,12-dimethylbenz(α)anthracene (DMBA) and were sacrificed 20 weeks later. HPLC-ECD, HPLC-UV and LC-MS were used. Obesity capable significantly modify methylation status in liver caused higher (p &amp;lt; 0.001) SAM/SAH ratio (know as “methylation ratio”) and increased (p &amp;lt; 0.05) global DNA methylation. Also, obesity decrease GSH/GSSG ratio (known as “oxidative stress ratio”) with p &amp;lt; 0.0001 inducing higher oxidative stress and as results, increase presence both oxidized guanosine (8-OH-Guanosine) with p &amp;lt; 0.001 and oxidized 5metylCytosine (5hmCytosine) p&amp;lt;0.04 in liver DNA. 8-OH-Guanosine/5hmCytosine ratio was not significantly affected. Obesity caused significant oxidative stress in liver, causing oxidative DNA damage and change of DNA methylation pattern. These changes may contribute to the development of fatty liver in breast cancer models. Citation Format: Reza Hakkak, Stepan Melnyk, Soheila Korourian. Obesity promotes liver pro-oxidative and DNA damage in mammary tumor of Zucker rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 740.
Abstract 4199: rhIL-7-hyFc (efineptakinalpha; NT-I7) enhances the anti-tumor response when combined with hIL-2/TCB2c complex
Authors: Seungtae Baek, Sun-Kyoung Im, Minji Lee, Mankyu Ji, Miyoung Kim, Daeun Kim, Jun Young Lee, Donghoon Choi
Journal: Cancer Research (2022)

Abstract rhIL-7-hyFc (efineptakin-alfa; NT-I7) is a potent T cell amplifier, with a homodimeric interleukin-7 (IL-7) fused to the hybridizing IgD/IgG4 immunoglobulin domain. Previous work has shown that in mice, NT-I7 dramatically increases tumor-infiltrating CD8+ T cells while reducing the frequency of PD-1+ CD8+ T cells in the tumor. There is also significant expansion of Central Memory (CM)-phenotype CD8+ T cells (CD62L+CD44+) in the tumor and tumor draining lymph node. Here, we investigated the anti-tumor effect of NT-I7 in combination with a T cell activator, SLC-3010 (hIL-2/TCB2c complex), in MC38 tumor-bearing mice. Because TCB2 is an antibody specific for IL-2 that blocks interaction of IL-2 and IL-2Rα (CD25), SLC-3010 can selectively activate T cells while disfavoring Treg activation. Mice were administered a single dose of NT-I7 or SLC-3010 via intramuscular or intravenous injection, respectively. The combination of NT-I7 with SLC-3010 enhanced the anti-tumor response with increased number and frequency of CD8+ T cells as well as granzyme B expression in the tumor. The number of CD8+ T cells peaked at day 4 and day 7 by SLC-3010 and NT-I7, respectively. The number of Tregs in the tumor was slightly increased by NT-I7 and SLC-3010, but it was not statistically significant. Interestingly, NT-I7, but not SLC-3010, increased the frequency of PD-1+TCF-1+TOX- stem-like CD8+ T cells in the draining lymph node. Meanwhile, SLC-3010 significantly increased the number of PD-1+ CD8+ T cells in the tumor. Our data suggests that NT-I7 can be applied in combination with other immunotherapies such as IL-2 to enhance the anti-tumor response. Citation Format: Seungtae Baek, Sun-Kyoung Im, Minji Lee, Mankyu Ji, Miyoung Kim, Daeun Kim, Jun Young Lee, Donghoon Choi. rhIL-7-hyFc (efineptakinalpha; NT-I7) enhances the anti-tumor response when combined with hIL-2/TCB2c complex [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4199.
Abstract 3437: Characterization of a potent and selective A2aR monoclonal antibody antagonist for the treatment of cancer
Authors: Changyun Hu, Jiandong Zhang, Shuying Liu, Xinyan Zhao
Journal: Cancer Research (2022)

Abstract Introduction: Adenosine-mediated suppression of anti-tumor immunity has been shown to be one of the mechanisms for immunosuppression and resistance to immune checkpoint blockade (ICB) therapies such as anti-PD-1 or anti-PD-L1 monoclonal antibodies (mAbs). Therapeutic candidates (biologics and small molecule inhibitors(SMIs)) targeting ectonucleotidases CD39 and CD73, enzymes responsible for hydrolyzing ATP to adenosine, and SMIs targeting adenosine receptors are currently under active preclinical and early clinical development. Here we present the characterization of a novel, selective anti-human A2aR antagonist mAb that showed high potency in inhibiting adenosine mediated immunosuppressive functions to enhance anti-tumor immunity. Methods: A panel of mAbs binding to human adenosine receptor A2aR (hA2aR) were generated via hybridoma technology. The specificity and cross-reactivity were measured by FACS using human A1R, A2aR, A2bR, A3R or mouse A2aR over-expressing cells, as well as human and cynomolgus monkey PBMC. The cellular potency of these mAbs was assessed by measuring decreased cAMP levels in engineered HEK293 cells stably over-expressing hA2aR, a Gs protein coupled receptor (GPCR), upon stimulation with agonist NECA. The ability of lead candidate AT-004 to reverse adenosine-mediated immune suppression of human CD8 T-cells was determined using standard CD3/CD28 activation conditions. The in vivo efficacy of humanized AT-004 is being evaluated using ICB treatment resistant solid tumor mouse models. Results: AT-004 represents a panel of novel, selective mAbs. These mAbs specifically bind to human A2aR, but not to family members including A1R, A2bR and A3R. Cross-reactivity to cynomolgus monkey PBMCs was also observed. AT-004 inhibited NECA-mediated A2aR activation with a potency over 100-fold higher than SMIs e.g. AZD4635. AT-004 significantly reversed the ability of adenosine to suppress CD8 T cell activation as indicated by restoration of cell surface marker expression and increased levels of cytokines such as IFN-γ in the supernatants. Conclusions: AT-004 is a potent, selective and highly potent antagonist of A2aR receptor. Considering its potential safety advantage as an mAb comparing to most known A2aR SMI antagonists in that it does not cross the blood brain barrier, AT-004 maybe a promising novel therapeutic candidate for immunotherapy, vital for enhancing anti-tumor responses in solid tumors that show an incomplete response or resistance to anti-PD-1 or anti-PD-L1 mAb treatment due to elevated adenosine level in tumor microenvironment (TME). Citation Format: Changyun Hu, Jiandong Zhang, Shuying Liu, Xinyan Zhao. Characterization of a potent and selective A2aR monoclonal antibody antagonist for the treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3437.
Abstract 5086: Effects of immune negative genes on immunotherapy combined anti-vascular for liver cancer
Authors: Xinhua Zhu, Yanan Chen, Junling Zhang, Mengli Huang, Xihua Xia
Journal: Cancer Research (2022)

Abstract Background: In recent years, the application of immune checkpoint inhibitors (ICIs) therapies targeting the programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) or cytotoxic T lymphocyte (CTLA-4) pathway represents a major breakthrough in many types of cancer. However, low response rates has limited the clinical application of ICIs monotherapy for liver cancer.Anti-vascular combined ICIs are the preferred regiments in first-line systemic treatment of hepatocellular carcinoma (HCC) by NCCN. Therefore, strategies to improve efficacy through patient stratification, biomarker-directed therapies or combinations remain urgently needed. The purpose of this study was to explore potential genomic markers associated with “low response rates” in liver cancer with ICIs combination therapy. Methods: Between July 2019 and April 2021, a total of 47 patients with advanced liver cancer treated with ICIs combined anti-vascular or anti-vascular alone therapy were admitted to Drum Tower Hospital. We retrospectively identified genomic markers, abstracted clinicopathologic features and treatment outcomes. Results: 47 patients with advanced liver cancer treated with immunotherapy combined anti-vascular or anti-vascular were included in this analysis. 40 of 47patients (85.1%) were male and the median age was 58 years (range, 32 to 80 years). Most patients (85.1%) were HCC and 12 patients had at least one immune negative gene mutation (including CCND1, FGF19, FGF3, FGF4, KEAP1, JAK1, MDM4, DNMT3A, EGFR and STK11). Median follow-up was 206 days in immunotherapy combined anti-vascular group and 215 days in anti-vascular group. In the immunotherapy combined anti-vascular group, compared with wild-type, patients with immune negative gene mutations were significantly associated with poorer overall survival (P=0.021). In anti-vascular alone group, there was no significant difference in median OS for patients with/without immune negative gene (P=0.94). In addition, patients with immune negative gene mutations, OS of anti-vascular alone was better than immunotherapy combined anti-vascular (P=0.085). Conclusion: Our study revealed that liver cancer with immune negative gene mutations have a worse prognosis than wild-type patients on immunotherapy combined anti-vascular. In addition, in patients with immune negative gene mutations, immunotherapy combined anti-vascular did not significantly improve prognosis compared to anti-vascular alone. Citation Format: Xinhua Zhu, Yanan Chen, Junling Zhang, Mengli Huang, Xihua Xia. Effects of immune negative genes on immunotherapy combined anti-vascular for liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5086.
Cerebellar dopamine D2 receptors regulate social behaviors
Authors: Laura Cutando, Emma Puighermanal, Laia Castell, Pauline Tarot, Morgane Belle, Federica Bertaso, Margarita Arango-Lievano, Fabrice Ango, Marcelo Rubinstein, Albert Quintana, Alain Chédotal, Manuel Mameli, Emmanuel Valjent
Journal: Nature Neuroscience (2022)
Abstract 3774: The effect of CDK5 on mitochondrial function in Glioblastoma Multiforme (GBM)
Authors: Adina Brett-Morris, Jason Mears, Kristy Rochon
Journal: Cancer Research (2022)

Abstract Glioblastoma Multiforme (GBM) is the most common and aggressive form of brain tumors.Despite conventional therapies, average patient survival is less than two years. GBMrecurrence is in part due to self-renewing tumor initiating cells, often called glioma stemcells (GSCs), which are characterized by their proliferation and tumor formation capacity,as well as their metabolic features. Thus, mitochondrial function represents a potentiallink between cellular metabolism and differentiation state. Mitochondrial fission isindispensable for growing and dividing cells. Dynamin-related protein 1 (Drp1) is essentialfor this process. In particular, there is cumulative evidence that links Drp1 with severaltypes of cancers, including GBM. Regulation of Drp1 is mainly controlled by post-translational modifications (PTMs). Importantly, recent studies have shown CDK5-dependent phosphorylation at the activating site serine 616 of Drp1 enhancesmitochondrial fission. CDK5 plays a crucial role in the central nervous system as well as,in tumor progression. Therefore, our lab hypothesized that inhibition of CDK5 would targetmitochondrial function in order to decrease tumor growth and sensitize brain tumors toconventional therapies. Western blot analysis has shown that CDK5-dependentphosphorylation of Drp1 is present in GSCs and GBM cell lines but absent in non-stemtumor cells (NSTC) and astrocytes. Small-molecule CDK5 inhibitors or CDK5 knockdownthrough siRNA in GSCs and GBM cell lines decreased activating phosphorylation of Drp1,leading to elongation of mitochondria morphology and corresponding reductions in cellviability and cell proliferation. Additionally, CDK5 inhibition showed sensitization toionizing radiation (IR) in GSCs and GBM cells. Importantly, CDK5 inhibition or knockdowncombined with IR, showed increased levels of cleaved caspase-7 and cleaved PARPsuggesting a role for apoptosis in decreased cell proliferation and sensitization to IR.Interestingly, CDK5 inhibition also diminished mitochondrial oxidative phosphorylation.Overall, these findings highlight an important role for CDK5 in regulating mitochondrialfunction in GBM, and targeting CDK5 offers a novel strategy to sensitize tumors to chemo-and radiotherapies. Citation Format: Adina Brett-Morris, Jason Mears, Kristy Rochon. The effect of CDK5 on mitochondrial function in Glioblastoma Multiforme (GBM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3774.
Abstract 5177: Lymph node ratio is superior to AJCC N stage for predicting recurrence in papillary thyroid carcinoma
Authors: Sandeep K. Parvathareddy, Abdul K. Siraj, Zeeshan Qadri, Saeeda O. Ahmed, Nabil Siraj, Felisa DeVera, Padmanaban Annaiyappanaidu, Maria A. Sabido, Wael Haqawi, Hassan Aldossari, Khawla S. Al-Kuraya
Journal: Cancer Research (2022)

Abstract Objective: Recently, lymph node ratio (LNR) has emerged as an alternative to American Joint Committee on Cancer (AJCC) N stage, with superior prognostic value. The utility of LNR in Middle Eastern Papillary thyroid carcinoma (PTC) remains unknown. Therefore, we retrospectively analyzed a large cohort of 1407 PTC patients for clinico-pathological associations of LNR. Methods: Receiver operating characteristics (ROC) curve was used to determine the cut-off for LNR. We also performed multivariate logistic regression analysis to determine whether LNR or AJCC N stage was superior in predicting recurrence in PTC. Results: Based on ROC curve analysis, a cut-off of 0.15 was chosen for LNR. High LNR was significantly associated with adverse clinico-pathological characteristics such as male sex, extrathyroidal extension, lymphovascular invasion, multifocality, bilateral tumors, T4 tumors, lateral lymph node (N1b) involvement, distant metastasis, advanced tumor stage, ATA high risk category and tumor recurrence. On multivariate analysis, we found that LNR was a better predictor of tumor recurrence than AJCC N stage (Odds ratio: 1.96 vs. 1.30; p value: 0.0184 vs. 0.3831). We also found that LNR combined with TNM stage and ATA risk category improved the prediction of recurrence-free survival, compared to TNM stage or ATA risk category alone. Conclusions: The present study suggests LNR is an independent predictor of recurrence in Middle Eastern PTC. Integration of LNR with 8th edition AJCC TNM staging system and ATA risk stratification will improve the accuracy to predict recurrence in Middle Eastern PTC and help in tailoring treatment and surveillance strategies in these patients. Citation Format: Sandeep K. Parvathareddy, Abdul K. Siraj, Zeeshan Qadri, Saeeda O. Ahmed, Nabil Siraj, Felisa DeVera, Padmanaban Annaiyappanaidu, Maria A. Sabido, Wael Haqawi, Hassan Aldossari, Khawla S. Al-Kuraya. Lymph node ratio is superior to AJCC N stage for predicting recurrence in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5177.